Neonatal hypofunction of NMDARs during early postnatal development does not interfere with the expression of LTP in the MPP – DG synapse.
We also explored the synaptic potentiation of the MPP from control and MK-801-treated slices with the same TBS protocol we delivered at the LPP synapse. A stable baseline response of MPP fEPSPs was recorded for 20 min. This was followed by TBS and 90 min of continuous recording and then, finally, perfusion of DCG-IV (5 µM). In the control slices, MPP TBS triggered a PTP and a robust, long-lasting enhancement of the MPP fEPSP slope, sensitive to DCG-IV (fEPSP at PTP: 199.8 ± 11.65% of baseline; fEPSP 90 min post-TBS: 171.4 ± 16% of baseline; fEPSP in presence of DCG-IV: 18.27 ± 2.24% of baseline; n = 8 slices / 7 animals; traces and black symbols in Figure 7a-b). Interestingly, MPP TBS delivered on the MK-801-treated slices also triggered PTP, followed by a sustained increase in the slope of the fEPSP not statistically different from the synaptic potentiation observed in the control slices (fEPSP at PTP: 198.9 ± 29.47% of baseline; fEPSP 90 min post-TBS: 135 ± 9.43% of baseline, Mann-Whitney test, P > 0.05 vs. control; fEPSP in presence of DCG-IV: 32.46 ± 5.16% of baseline;n = 7 slices / 7 animals; traces and red symbols in Figure 7a-b). Likewise, we did not find differences in 𝜏 values between the control and MK-801-treated slices (𝜏 in control: 65 ± 3 s; 𝜏 in MK-801: 83.94 ± 16.34 s, Mann-Whitney test, P > 0.05: inset in Figure 7b).
The average post-TBS responses at 90 min for the slices analyzed in the control condition and MK-801-treated slices are depicted in the bar graphs in Figure 7c. The heatmaps in Figure 7d contrast the magnitude of the synaptic potentiation obtained in each slice, and the cumulative probability graph in Figure 7e shows the potentiation for control slices (black symbols) vs. MK-801-treated slices (red symbols). These results suggest that transient hypofunction of NMDA receptors during early postnatal development does not suppress the MPP – DG synapse’s ability to undergo LTP in young rats.